The influence of the hypothalamic releasing factors CRF and GRF on the hormonal secretion of pituitary adenomas has been determined in vitro and correlated with the patients' response in vivo. These studies indicate that the pituitary tumors causing Cushing's disease, Nelson's Syndrome and acromegaly are responsive to their appropriate releasing factor. We are investigating the potential of using the releasing factors conjugated to toxic proteins to effect cytotoxicity of pituitary tumors in vitro. The preliminary results are encouraging. We have also investigated the use of venous sampling to aid in the diagnosis and treatment of patients with Cushing's syndrome. Our results, which now include 55 patients with Cushing's syndrome, suggest that the procedure will be of significant benefit in: 1) establishing the diagnosis of Cushing's disease and 2) determining preoperatively the site of pituitary microadenomas.